Clinical and Analytical Validation of Cancer Biomarkers

 描述（由申请方提供）：本提案是对我们位于约翰霍普金斯医院约翰霍普金斯医学实验室（JHML）临床化学部（CCD）内的EDRN生物标志物参考实验室（BRL）的更新。BRL将继续作为生物标志物临床和实验室验证的网络资源，包括技术开发和分析改进。JHML由美国病理学家学院（CAP）认证，并由CLIA（1988年临床实验室改进修正案）监管。因此，JHML在质量控制和质量保证方面遵循严格的药物非临床研究质量管理规范（GLP）指南。拟定产品开发将在约翰霍普金斯大学生物标志物发现和转化中心（CBDT）进行。该项目的目标是验证血清蛋白质组生物标志物，包括我们目前的EDRN BRL发育研究中发现的两种生物标志物，用于前列腺活检前预测男性侵袭性前列腺癌。产品“AGPC”是一种体外诊断多变量指数测定（IVDMIA），其将一组生物标志物组合成单值数值指数评分。我们组建了一支强大的研究和临床科学家团队，他们在癌症生物标志物以及技术开发、研究设计、生物信息学、验证和翻译方面拥有多年经验。首席研究员陈博士是CCD和CBDT的总监。他在临床化学方面拥有30多年的经验，并进行了许多（> 75）由行业资助的癌症诊断研究，获得了FDA的批准。自2000年EDRN成立以来，已有五种EDRN开发的检测试剂盒获得FDA批准用于临床。在这五个实验室中，我们的BRL领导了卵巢癌血清OVA 1、前列腺癌血清proPSA（phi）的开发，并作为前列腺癌尿液PCA 3研究的参考实验室。事实上，基于我们在《癌症研究》上发表的原始多重蛋白质组学研究的OVA 1是FDA批准用于临床的第一个蛋白质组学IVDMIA。此外，三家领先的诊断/生物技术公司已同意在我们的产品开发提案中与我们合作。在此次更新中，我们计划通过网络合作继续坚定地致力于EDRN使命，并在生物标志物验证、技术/检测改进和产品开发方面发挥领导作用。有了这个多学科的科学家团队，约翰霍普金斯的BRL为癌症生物标志物验证的成功提供了最好的机会，并将其转化为癌症早期检测的临床。

 DESCRIPTION (provided by applicant): This proposal is a renewal of our EDRN Biomarker Reference Laboratory (BRL) which is located within the Clinical Chemistry Division (CCD) of the Johns Hopkins Medical Laboratories (JHML) at the Johns Hopkins Hospital. The BRL will continue to serve as a network resource for clinical and laboratory validation of biomarkers, which includes technological development and assay refinement. The JHML are certified by the College of American Pathologist (CAP) and regulated by CLIA (Clinical Laboratory Improvement Amendments of 1988). As such, the JHML follow stringent, good laboratory practice (GLP) guidelines for quality control and quality assurance. The proposed product development will be conducted at the Center for Biomarker Discovery and Translation (CBDT) at The Johns Hopkins University. The project goal is to validate serum proteomic biomarkers, including two biomarkers discovered in our current EDRN BRL developmental study, for the prediction of aggressive prostate cancer in men prior to prostate biopsy. The product "AGPC" is an in vitro diagnostic multivariate index assay (IVDMIA) that combines a panel of biomarkers into a single-valued numerical index score. We have assembled a strong team of research and clinical scientists with many years of experience with cancer biomarkers and in technology development, study design, bioinformatics, validation, and translation. Dr. Chan, the PI, is the Director of both CCD and CBDT. He has over 30 years of experience in clinical chemistry and has conducted many (> 75) research studies funded by industry on cancer diagnostics leading to the approval by the FDA. Since the inception of the EDRN in 2000, five EDRN developed assays have been approved by the FDA for clinical use. Of these five, our BRL led the development of serum OVA1 for ovarian cancer, serum proPSA (phi) for prostate cancer, and served as the reference lab for the urine PCA3 study for prostate cancer. In fact, OVA1 which is based on our original multiplex proteomic study published in Cancer Research, was the first proteomic IVDMIA ever cleared by the FDA for clinical use. In addition, three leading diagnostics/biotechnology companies have agreed to collaborate with us in our product development proposal. In this renewal, we plan to continue our strong commitment to the EDRN mission through network collaborations, and provide leadership in biomarker validation, technology/assay improvement, and product development. With this multi-disciplinary team of scientists, the BRL at Johns Hopkins offers the best opportunity for the success of cancer biomarker validation and translation into the clinic for the early detection of cancer.